Prevalence, Risk Factors, and Outcomes of Influenza-Associated Neurologic Complications in Children.

OBJECTIVE: To determine the frequency of neurologic complications associated with influenza in hospitalized children. STUD DESIGN: We performed a cross-sectional study of children (2 months through 17 years of age) with influenza discharged from 49 children's hospitals in the Pediatric Health Information System during the influenza seasons of 2015-2020. Neurologic complications were defined as encephalopathy, encephalitis, aseptic meningitis, febrile seizure, nonfebrile seizure, brain abscess and bacterial meningitis, Reye syndrome, and cerebral infarction. We assessed length of stay (LOS), intensive care unit (ICU) admission, ICU LOS, 30-day hospital readmissions, deaths, and hospital costs associated with these events. Patient-level risk factors associated with neurologic complications were identified using multivariable logistic regression. RESULTS: Of 29 676 children hospitalized with influenza, 2246 (7.6%) had a concurrent diagnosis of a neurologic complication; the most frequent were febrile seizures (5.0%), encephalopathy (1.7%), and nonfebrile seizures (1.2%). Hospital LOS, ICU admission, ICU LOS, deaths, and hospital costs were greater in children with neurologic complications compared with those without complications. Risk factors associated with neurologic complications included male sex (aOR 1.1, 95% CI 1.02-1.21), Asian race/ethnicity (aOR 1.7, 95% CI 1.4-2.1) (compared with non-Hispanic White), and the presence of a chronic neurologic condition (aOR 3.7, 95% CI 3.1-4.2). CONCLUSIONS: Neurologic complications are common in children hospitalized with influenza, especially among those with chronic neurologic conditions, and are associated with worse outcomes compared with children without neurologic complications. These findings emphasize the strategic importance of influenza immunization and treatment, especially in high-risk populations.

Prevalence of Clinically Significant Drug-Drug Interactions Across US Children's Hospitals.

BACKGROUND: Little is known about the prescribing of medications with potential drug-drug interactions (DDIs) in the pediatric population. The objective of this study was to determine the prevalence and variation of prescribing medications with clinically significant DDIs across children's hospitals in the United States. METHODS: We performed a retrospective cohort study of patients <26 years of age who were discharged from 1 of 52 US children's hospitals between January 2016 and December 2018. Fifty-three drug pairings with clinically significant DDIs in children were evaluated. We identified patient-level risk factors associated with DDI using multivariable logistic regression. Adjusted hospital-level rates of DDI exposure were derived by using a generalized linear mixed-effects model, and DDI exposure variations were examined across individual hospitals. RESULTS: Across 52 children's hospitals, 47 414 (2.0%) hospitalizations included exposure to a DDI pairing (34.9 per 1000 patient-days) during the study period. One-quarter of pairings were considered contraindicated (risk grade X). After adjusting for hospital and clinical factors, there was wide variation in the percentage of DDI prescribing across hospitals, ranging from 1.05% to 4.92%. There was also substantial hospital-level variation of exposures to individual drug pairings. Increasing age, number of complex chronic conditions, length of stay, and surgical encounters were independently associated with an increased odds of DDI exposure. CONCLUSIONS: Patients hospitalized at US children's hospitals are frequently exposed to medications with clinically significant DDIs. Exposure risk varied substantially across hospitals. Further study is needed to determine the rate of adverse events due to DDI exposures and factors amenable for interventions promoting safer medication use.

A Prediction Model to Identify Febrile Infants ≤60 Days at Low Risk of Invasive Bacterial Infection.

OBJECTIVES: To derive and internally validate a prediction model for the identification of febrile infants ≤60 days old at low probability of invasive bacterial infection (IBI). METHODS: We conducted a case-control study of febrile infants ≤60 days old who presented to the emergency departments of 11 hospitals between July 1, 2011 and June 30, 2016. Infants with IBI, defined by growth of a pathogen in blood (bacteremia) and/or cerebrospinal fluid (bacterial meningitis), were matched by hospital and date of visit to 2 control patients without IBI. Ill-appearing infants and those with complex chronic conditions were excluded. Predictors of IBI were identified with multiple logistic regression and internally validated with 10-fold cross-validation, and an IBI score was calculated. RESULTS: We included 181 infants with IBI (155 [85.6%] with bacteremia without meningitis and 26 [14.4%] with bacterial meningitis) and 362 control patients. Twenty-three infants with IBI (12.7%) and 138 control patients (38.1%) had fever by history only. Four predictors of IBI were identified (area under the curve 0.83 [95% confidence interval (CI): 0.79-0.86]) and incorporated into an IBI score: age <21 days (1 point), highest temperature recorded in the emergency department 38.0-38.4°C (2 points) or ≥38.5°C (4 points), absolute neutrophil count ≥5185 cells per µL (2 points), and abnormal urinalysis results (3 points). The sensitivity and specificity of a score ≥2 were 98.8% (95% CI: 95.7%-99.9%) and 31.3% (95% CI: 26.3%-36.6%), respectively. All 26 infants with meningitis had scores ≥2. CONCLUSIONS: Infants ≤60 days old with fever by history only, a normal urinalysis result, and an absolute neutrophil count <5185 cells per µL have a low probability of IBI.

Application of the Rochester Criteria to Identify Febrile Infants With Bacteremia and Meningitis.

OBJECTIVES: The Rochester criteria were developed to identify febrile infants aged 60 days or younger at low-risk of bacterial infection and do not include cerebrospinal fluid (CSF) testing. Prior studies have not specifically assessed criteria performance for bacteremia and bacterial meningitis (invasive bacterial infection). Our objective was to determine the sensitivity of the Rochester criteria for detection of invasive bacterial infection. METHODS: Retrospective cohort study of febrile infants aged 60 days or younger with invasive bacterial infections evaluated at 8 pediatric emergency departments from July 1, 2012, to June 30, 2014. Potential cases were identified from the Pediatric Health Information System using International Classification of Diseases, Ninth Revision diagnosis codes for bacteremia, meningitis, urinary tract infection, and fever. Medical record review was then performed to confirm presence of an invasive bacterial infection and to evaluate the Rochester criteria: medical history, symptoms or ill appearance, results of urinalysis, complete blood count, CSF testing (if obtained), and blood, urine, and CSF culture. An invasive bacterial infection was defined as growth of pathogenic bacteria from blood or CSF culture. RESULTS: Among 82 febrile infants aged 60 days or younger with invasive bacterial infection, the sensitivity of the Rochester criteria were 92.7% (95% confidence interval [CI], 84.9%-96.6%) overall, 91.7% (95% CI, 80.5%-96.7%) for neonates 28 days or younger, and 94.1% (95% CI, 80.9%-98.4%) for infants aged 29 to 60 days old. Six infants with bacteremia, including 1 neonate with bacterial meningitis, met low-risk criteria. CONCLUSIONS: The Rochester criteria identified 92% of infants aged 60 days or younger with invasive bacterial infection. However, 1 neonate 28 days or younger with meningitis was classified as low-risk.

Epidemiology and Etiology of Invasive Bacterial Infection in Infants ≤60 Days Old Treated in Emergency Departments.

OBJECTIVES: To help guide empiric treatment of infants ≤60 days old with suspected invasive bacterial infection by describing pathogens and their antimicrobial susceptibilities. STUDY DESIGN: Cross-sectional study of infants ≤60 days old with invasive bacterial infection (bacteremia and/or bacterial meningitis) evaluated in the emergency departments of 11 children's hospitals between July 1, 2011 and June 30, 2016. Each site's microbiology laboratory database or electronic medical record system was queried to identify infants from whom a bacterial pathogen was isolated from either blood or cerebrospinal fluid. Medical records of these infants were reviewed to confirm the presence of a pathogen and to obtain demographic, clinical, and laboratory data. RESULTS: Of the 442 infants with invasive bacterial infection, 353 (79.9%) had bacteremia without meningitis, 64 (14.5%) had bacterial meningitis with bacteremia, and 25 (5.7%) had bacterial meningitis without bacteremia. The peak number of cases of invasive bacterial infection occurred in the second week of life; 364 (82.4%) infants were febrile. Group B streptococcus was the most common pathogen identified (36.7%), followed by Escherichia coli (30.8%), Staphylococcus aureus (9.7%), and Enterococcus spp (6.6%). Overall, 96.8% of pathogens were susceptible to ampicillin plus a third-generation cephalosporin, 96.0% to ampicillin plus gentamicin, and 89.2% to third-generation cephalosporins alone. CONCLUSIONS: For most infants ≤60 days old evaluated in a pediatric emergency department for suspected invasive bacterial infection, the combination of ampicillin plus either gentamicin or a third-generation cephalosporin is an appropriate empiric antimicrobial treatment regimen. Of the pathogens isolated from infants with invasive bacterial infection, 11% were resistant to third-generation cephalosporins alone.

Empiric Antibiotic Use and Susceptibility in Infants With Bacterial Infections: A Multicenter Retrospective Cohort Study.

OBJECTIVES: To assess hospital differences in empirical antibiotic use, bacterial epidemiology, and antimicrobial susceptibility for common antibiotic regimens among young infants with urinary tract infection (UTI), bacteremia, or bacterial meningitis. METHODS: We reviewed medical records from infants <90 days old presenting to 8 US children's hospitals with UTI, bacteremia, or meningitis. We used the Pediatric Health Information System database to identify cases and empirical antibiotic use and medical record review to determine infection, pathogen, and antimicrobial susceptibility patterns. We compared hospital-level differences in antimicrobial use, pathogen, infection site, and antimicrobial susceptibility. RESULTS: We identified 470 infants with bacterial infections: 362 (77%) with UTI alone and 108 (23%) with meningitis or bacteremia. Infection type did not differ across hospitals (P = .85). Empirical antibiotic use varied across hospitals (P < .01), although antimicrobial susceptibility patterns for common empirical regimens were similar. A third-generation cephalosporin would have empirically treated 90% of all ages, 89% in 7- to 28-day-olds, and 91% in 29- to 89-day-olds. The addition of ampicillin would have improved coverage in only 4 cases of bacteremia and meningitis. Ampicillin plus gentamicin would have treated 95%, 89%, and 97% in these age groups, respectively. CONCLUSIONS: Empirical antibiotic use differed across regionally diverse US children's hospitals in infants <90 days old with UTI, bacteremia, or meningitis. Antimicrobial susceptibility to common antibiotic regimens was similar across hospitals, and adding ampicillin to a third-generation cephalosporin minimally improves coverage. Our findings support incorporating empirical antibiotic recommendations into national guidelines for infants with suspected bacterial infection.

Accuracy of diagnosis codes to identify febrile young infants using administrative data.

BACKGROUND: Administrative data can be used to determine optimal management of febrile infants and aid clinical practice guideline development. OBJECTIVE: Determine the most accurate International Classification of Diseases, Ninth Revision (ICD-9) diagnosis coding strategies for identification of febrile infants. DESIGN: Retrospective cross-sectional study. SETTING: Eight emergency departments in the Pediatric Health Information System. PATIENTS: Infants aged <90 days evaluated between July 1, 2012 and June 30, 2013 were randomly selected for medical record review from 1 of 4 ICD-9 diagnosis code groups: (1) discharge diagnosis of fever, (2) admission diagnosis of fever without discharge diagnosis of fever, (3) discharge diagnosis of serious infection without diagnosis of fever, and (4) no diagnosis of fever or serious infection. EXPOSURE: The ICD-9 diagnosis code groups were compared in 4 case-identification algorithms to a reference standard of fever ≥100.4°F documented in the medical record. MEASUREMENTS: Algorithm predictive accuracy was measured using sensitivity, specificity, and negative and positive predictive values. RESULTS: Among 1790 medical records reviewed, 766 (42.8%) infants had fever. Discharge diagnosis of fever demonstrated high specificity (98.2%, 95% confidence interval [CI]: 97.8-98.6) but low sensitivity (53.2%, 95% CI: 50.0-56.4). A case-identification algorithm of admission or discharge diagnosis of fever exhibited higher sensitivity (71.1%, 95% CI: 68.2-74.0), similar specificity (97.7%, 95% CI: 97.3-98.1), and the highest positive predictive value (86.9%, 95% CI: 84.5-89.3). CONCLUSIONS: A case-identification strategy that includes admission or discharge diagnosis of fever should be considered for febrile infant studies using administrative data, though underclassification of patients is a potential limitation.

Pediatric hospitalist perceptions regarding trainees' effects on cost and quality of care.

OBJECTIVE: To determine pediatric hospitalists' perceptions about residents' effects on cost and quality of care and their own ability to provide and teach cost-effective, high-quality care. METHODS: A 15-item survey assessing hospitalist perceptions of resident impact on costs/quality and their role in teaching cost-effectiveness was developed and sent to 180 hospitalists from 113 institutions in the United States. RESULTS: Of 180 hospitalists surveyed, 127 completed surveys (71%). Overall, 76 (60%) and 91 (72%) hospitalists believed that residents increase quality and cost of care, respectively. Respondents who worked with residents all the time were more likely to state that residents increase quality (50 of 70 [71%]) compared with those who worked with residents sometimes (18 of 42 [43%]) or never (8 of 15 [53%]; P=.01). Similarly, academic hospitalists were more likely than community hospitalists to believe that residents increase quality (67 of 103 [65%] vs 9 of 24 [38%]; P=.03). Although only 28 (22%) respondents reported receiving formal cost-effectiveness training, 116 (91%) believed that they provided cost-effective care, and 103 (81%) believed that they were qualified to teach this topic. Most respondents (n=115 [91%]) believed that residents should participate in a cost-effectiveness curriculum. CONCLUSIONS: Most respondents felt trainees increase both the costs and quality of care for hospitalized children. The perception of increased quality was associated with increased resident interaction, whereas cost perceptions were similar across groups. Pediatric hospitalists report a lack of formal cost-effectivesness training, but nearly all respondents supported the incorporation of such training into graduate medical education programs.

Association of clinical practice guidelines with emergency department management of febrile infants ≤56 days of age.

BACKGROUND: Differences among febrile infant institutional clinical practice guidelines (CPGs) may contribute to practice variation and increased healthcare costs. OBJECTIVE: Determine the association between pediatric emergency department (ED) CPGs and laboratory testing, hospitalization, ceftriaxone use, and costs in febrile infants. DESIGN: Retrospective cross-sectional study in 2013. SETTING: Thirty-three hospitals in the Pediatric Health Information System. PATIENTS: Infants aged ≤56 days with a diagnosis of fever. EXPOSURES: The presence and content of ED-based febrile infant CPGs assessed by electronic survey. MEASUREMENTS: Using generalized estimating equations, we evaluated the association between CPG recommendations and rates of urine, blood, cerebrospinal fluid (CSF) testing, hospitalization, and ceftriaxone use at ED discharge in 2 age groups: ≤28 days and 29 to 56 days. We also assessed CPG impact on healthcare costs. RESULTS: We included 9377 ED visits; 21 of 33 EDs (63.6%) had a CPG. For neonates ≤28 days, CPG recommendations did not vary and were not associated with differences in testing, hospitalization, or costs. Among infants 29 to 56 days, CPG recommendations for CSF testing and ceftriaxone use varied. CSF testing occurred less often at EDs with CPGs recommending limited testing compared to hospitals without CPGs (adjusted odds ratio: 0.5, 95% confidence interval: 0.3-0.8). Ceftriaxone use at ED discharge varied significantly based on CPG recommendations. Costs were higher for admitted and discharged infants 29 to 56 days old at hospitals with CPGs. CONCLUSIONS: CPG recommendations for febrile infants 29 to 56 days old vary across institutions for CSF testing and ceftriaxone use, correlating with observed practice variation. CPGs were not associated with lower healthcare costs.